CREST-2 Shows Reduced Stroke Risk With Carotid Artery Stenting Plus Intensive Medical Management; No Added Benefit Seen With CEA

November 21, 2025—In a pair of randomized, observer-blinded clinical trials designed to evaluate optimal management of asymptomatic carotid stenosis, Brott et al found that carotid artery stenting (CAS) added to intensive medical therapy significantly reduced stroke risk compared with medical therapy alone, while carotid endarterectomy (CEA) offered no significant additional benefit. Results of the CREST-2 trials were presented at the Society of Vascular and Interventional Neurology annual meeting and the VEITHsymposium and published in The New England Journal of Medicine.¹

Investigators conducted two parallel studies enrolling 2,485 patients (mean age, 70 years; 37% women) with ≥ 70% asymptomatic carotid stenosis across 155 international centers. Participants were randomized either to intensive medical management alone or to CAS plus medical therapy (n = 1,245) or CEA plus medical therapy (n = 1,240). The primary outcome was a composite of any stroke or death within 44 days or ipsilateral ischemic stroke up to 4 years postrandomization. Strokes were classified as major or minor, disabling or nondisabling, and ischemic or hemorrhagic by a stroke adjudication committee blinded to treatment assignments.

The intensive medical management program targeted systolic blood pressure < 130 mm Hg and low-density lipoprotein cholesterol < 70 mg/dL, alongside glucose control, smoking cessation, and weight management. Health coaching and pharmacologic support (including PCSK9 inhibitors) were provided to optimize adherence. All operators performing revascularization were required to have documented periprocedural stroke and death rates below 3%.

At 4 years, the CAS trial demonstrated a 6.0% event rate with medical therapy alone versus 2.8% with CAS (absolute risk difference, 3.2 percentage points; 95% CI, 0.6-5.9; P = .02), corresponding to a number needed to treat of 31 to prevent one composite event. The CEA trial reported an event rate of 5.3% versus 3.7% for medical therapy alone and CEA, respectively (absolute risk difference, 1.6 percentage points; 95% CI, –1.1 to 4.3; P = .24). In both trials, disabling stroke rates were low across all groups, and benefits of CAS were consistent across subgroups, including age, sex, and comorbidity categories.

During the periprocedural period (0-44 days), no strokes or deaths occurred in the medical therapy alone group in the CAS trial, while eight events (seven strokes, one death) occurred in the CAS group. In the CEA trial, three strokes occurred in medical therapy patients versus nine strokes in CEA patients. Beyond 44 days in the CAS trial, annual event rates were 1.7% with medical therapy and 0.4% with CAS, representing a fourfold risk reduction (relative risk, 4.07; 95% CI, 1.78-9.31). For this time period in the CEA trial, annual event rates were 1.3% for the medical therapy group versus 0.5% for the CEA group (relative risk, 2.38; 95% CI, 1.13-5.00).

Investigators noted that all groups benefited from rigorous medical optimization, with over 70% achieving target blood pressure and lipid levels by 12 months. Limitations included evolving medical guidelines during follow-up, the exclusion of transcarotid artery revascularization, and restriction to high-volume, experienced centers.

These parallel CREST-2 trials demonstrated that CAS plus intensive medical therapy significantly reduced stroke risk compared with medical therapy alone in patients with asymptomatic high-grade carotid stenosis, whereas the addition of CEA offered no clear advantage. The findings reinforce the value of modern medical therapy and highlight the importance of operator experience and patient selection in carotid revascularization strategies.

“With the CREST-2 trial, carotid stenting with embolism protection should become the first-line consideration for preventing stroke when added to intensive medical management, provided the anatomy is suited for the procedure and the operator has the requisite skill,” said investigator James F. Meschia, MD, in comments to Endovascular Today. Dr. Meschia, vascular neurologist and past Chair of the Department of Neurology at Mayo Clinic in Jacksonville, Florida, added that stenting does not change the need for intensive medical management.

“The CREST-2 results demonstrated that intensive medical therapy can exert a robust effect in reducing long-term stroke risk compared to historical outcomes,” said William A. Gray, MD, MSCAI, FACC, System Chief of the Cardiovascular Division at Main Line Health in Wynnewood, Pennsylvania. “And even with this, carotid stenting more than halved the stroke risk at 4 years—providing remarkable guidance and benefit for our patients.”

Looking ahead to how CREST-2 might inform the next major carotid trials, Dr. Meschia commented, “Stenting with embolic protection has proven itself for the classical indication of high-grade asymptomatic stenosis. The so-called vulnerable nonstenotic plaque may be an opportunity, but there will need to be more standardization and proof of reliability of markers of vulnerability before a definitive trial could be launched.”

1.  Brott TG, Howard G, Lal BK, et al. Medical management and revascularization for asymptomatic carotid stenosis. N Engl J Med. Published November 21, 2025. doi: 10.1056/NEJMoa2508800